Clinical Trial for GALNT14 Genotype - Guided, Sorafenib in Combination With TACE in Hepatocellular Carcinoma

February 4, 2020 updated by: Chang Gung Memorial Hospital

Randomized, Open Label, Clinical Trial for GALNT14 Genotype - Guided, Sorafenib in Combination With TACE Therapy in Hepatocellular Carcinoma

Transcatheter arterial chemoembolization (TACE) + sorafenib therapy has been demonstrated to exert a beneficial effective on time-to-tumor-progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) in some studies. However, the beneficial effect varies among studies conducted in different areas of the world. The objectives of this study are (1) to understand whether GALNT14 TT genotype patients respond better than do GALNT14 non-TT genotype patients when treated by TACE; and (2) to understand whether GALNT14 non-TT genotype patients can benefit from TACE plus sorafenib (Nexavar) combination therapy. Patients enrolled will be stratified by GALNT14 genotyping. The GALNT14 "non-TT" patients were then randomized into two subgroups to evaluate the safety, tolerability and efficacy of TACE plus sorafenib therapy.

The primary endpoint of this study is the efficacy of TACE with or without sorafenib combination therapy evaluated by complete remission (CR).

The secondary endpoints are:

  1. Time to partial or complete response (PR + CR).
  2. Time-to-tumor-progression (TTP) and the progression free survival (PFS).
  3. Overall survival (OS).
  4. Safety and tolerability of TACE plus sorafenib therapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The strategy of TACE + sorafenib is now being intensively investigated. It is a safe approach with significant beneficial effect on TTP in some studies, but the beneficial effect on OS remains uncertain. In the present study, we hypothesized that the GALNT14 genotype might play a role in this issue. Our pilot study indicated that GALNT14 "TT" genotype was associated with a favorable complete response rate in patients treated by TACE alone. This genotype was present in ~ 25% of Chinese population coming from Taiwan, Colorado (US), or Beijing (China), and in ~ 7% of Italian population. But it was present in ~ 50% of Japanese population. The lower percentage of a TACE - favorable genotype in Chinese and Italian population could explain the different results between Japanese and Chinese/Italian clinical trials. It is possible that in a population with higher percentage of TACE - favorable genotype (GALNT14 "TT"), the beneficial effect of sorafenib adjuvant treatment might not be detected. In this study, we proposed to examine the TACE + sorafenib effect in patients with GALNT14 "non-TT" genotype, a TACE - unfavorable genotype.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taoyuan, Taiwan
        • Chang Gung Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Confirmed Diagnosis of HCC:

    Cirrhotic subjects: Clinical diagnosis by AASLD criteria HCC can be defined in cirrhotic subjects by one imaging technique (CT scan, MRI, or second generation contrast ultrasound) showing a nodule larger than 2cm with contrast uptake in the arterial phase and washout in venous or late phases, or two imaging techniques showing this radiological behaviour for nodules of 1-2cm in diameter Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria

    Non-cirrhotic subjects:

    For subjects without cirrhosis, histological confirmation is mandatory Documentation of original biopsy for diagnosis is acceptable

  2. Never received TACE/ chemotherapy/ radiotherapy or targeted agents prior to this study.
  3. Patients should be either in BCLC clinical stage B (multinodular asymptomatic tumors without extra-hepatic spread or portal vein invasion) with or without unilateral secondary or tertiary branches of portal vein invasion. Main portal vein invasion or extra-hepatic spread is not allowed.
  4. Child-Pugh functional class A or B.
  5. Measurable disease using mRECIST criteria. At least 1 measurable lesion must be present.
  6. ECOG performance status 0 to 1.
  7. Age > 18 years
  8. Both men and women enrolled in this trial must use adequate birth control measures during the course of the trial and 4 weeks after the completion of trial
  9. Informed consent must be obtained prior to study initiation.
  10. Total bilirubin < 3.0 mg/dL with no evidence of biliary tract obstruction.
  11. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 × upper limit of normal.
  12. Absolute neutrophil count > 1000/mm3; Platelets ≧ 60x109/L.
  13. Serum creatinine < 2 x ULN.
  14. Antiviral treatment for hepatitis B or C is allowed except for interferon.

Exclusion Criteria:

  1. BCLC stage A.
  2. Presence of extrahepatic metastasis.
  3. Child-Pugh score =C
  4. Significant cardiac disease.
  5. Serious bacteria infection requiring systemic antibiotics.
  6. Pregnancy
  7. Expected non-compliance.
  8. Uncontrolled illness including, but not limited to, ongoing infection, congestive hear failure, unstable angina pectoris, cardiac arryhythmia, or psychiatric illness.
  9. Bleeding esophageal or gastric varices within three months without ligation or sclerosis injection therapy.
  10. Subjects with known HIV infection.
  11. ECOG status > or = 2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: GALNT14 TT
Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued.
Procedure: TACE
Transcatheter arterial chemoembolization was performed by the injection of small embolic particles coated with chemotherapeutic agents selectively into an artery directly supplying a tumor.
Other Names:
  • Transcatheter arterial chemoembolization
Active Comparator: GALNT14 non-TT TACE alone
Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued.
Procedure: TACE
Transcatheter arterial chemoembolization was performed by the injection of small embolic particles coated with chemotherapeutic agents selectively into an artery directly supplying a tumor.
Other Names:
  • Transcatheter arterial chemoembolization
Experimental: GALNT14 non-TT TACE plus sorafenib
Patients will be treated by Transcatheter arterial chemoembolization every 12 ± 2 weeks dependent on CT evaluation, plus sorafenib adjuvant therapy. Before each TACE, dynamic CT will be performed for pre-treatment evaluation. When no viable tumor is seen on CT, TACE is to be discontinued. patients will receive sorafenib 400 mg/d between each TACE. Patient will start receiving Sorafenib on Day 4 (up to Day 7) after 1st TACE (Day 1) and will interrupt after evening dose 4 days before each next TACE and re-start Sorafenib on Day 4 (up to Day 7) after each TACE cycle.Additional sorafenib treatment is optional and will be judged by investigator in the subject's best medical interest.
Procedure: TACE
Transcatheter arterial chemoembolization was performed by the injection of small embolic particles coated with chemotherapeutic agents selectively into an artery directly supplying a tumor.
Other Names:
  • Transcatheter arterial chemoembolization
Drug: sorafenib
sorafenib is an oral, multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma
Other Names:
  • Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete remission
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 3 years
3 years
Time to partial (including complete) response
Time Frame: 3 years
3 years
Time-to-tumor-progression (TTP)
Time Frame: 3 years
3 years
Progression free survival (PFS).
Time Frame: 3 years
3 years
Safety and tolerability of TACE plus sorafenib therapy recorded and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Investigators

  • Principal Investigator: Chau-Ting Yeh, MD/PhD, Chang Gung Memorial Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

July 1, 2021

Study Registration Dates

First Submitted

July 16, 2015

First Submitted That Met QC Criteria

July 20, 2015

First Posted (Estimate)

July 22, 2015

Study Record Updates

Last Update Posted (Actual)

February 5, 2020

Last Update Submitted That Met QC Criteria

February 4, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 104-1686A3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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